tbuckley/cabot-search huggingface dataset:
Abstract P324: Female Reproductive Factors and Risk of Type 2 Diabetes and Cardiovascular Disease Among Women With a History of Gestational Diabetes
Authors: Anna Birukov, Marta Guasch, Deirdre K Tobias, Sylvia H Ley, Clemens Wittenbecher, Jiaxi Yang, Joann E Manson, Jorge Chavarro, Frank B Hu, Cuilin Zhang
Journal: Circulation (2023)

Introduction: The link between gestational diabetes mellitus (GDM) and long-term risk of type 2 diabetes (T2D) and cardiovascular disease (CVD) is well established; however, risk factors underlying the progression of disease remain uncertain. Hypothesis: Female reproductive factors including ages at menarche, menopause, and first birth, number of live births, and surgically-induced menopause (uni- or bilateral oophorectomy or hysterectomy) are associated with higher risk of progression, while breastfeeding is associated with lower risk of progression from GDM to T2D/CVD. Methods: Participants in the Nurses’ Health Study II reported reproductive history at cohort baseline and over follow-up, including 5346 women with a history of GDM. Self-reported incident T2D or CVD (myocardial infarction, coronary revascularization or stroke) were confirmed via questionnaire or medical records. We estimated the hazard ratios (HR [95%]) across quintiles of each reproductive factor with incident T2D and CVD using Cox models adjusting for age, race/ethnicity, smoking, BMI at 18 years, physical activity, family history of T2D or CVD, alcohol intake, menopausal status, aspirin use, and Alternate Healthy Eating Index. Results: We documented 988 incident T2D and 149 CVD cases over 25 years of follow-up. In adjusted models, higher total lactation duration was associated with lower risk of T2D (5 categories: 0, 1-6, 7-12, 13-24, &gt;24 months, p for trend=0.01; highest vs. lowest category: HR 0.77 [95%CI: 0.60, 0.98]) and CVD (p for trend=0.03, HR 0.39 [95%CI: 0.19, 0.80]). Early age at menarche was linearly associated with higher risk of T2D (5 categories: ≤11, 12, 13, 14, &gt;14 y: p for trend &lt;0.0001), lowest (≤11 y) vs. reference (13 y) category: HR 1.28 [95%CI: 1.06, 1.53], while no trend could be observed for CVD outcomes (p for trend=0.48). Higher age at 1 st birth was associated with lower CVD risk (5 categories: &lt;23, 23-25 [reference], 26-29, 30-34, ≥35 y, p for trend=0.001; highest vs reference category: HR 0.17 [95%CI: 0.05, 0.57]), but not T2D). Compared with natural menopause, surgically induced menopause was associated with higher T2D risk: 1.32 (1.00, 1.73). Number of live births and age at menopause were not associated with T2D or CVD among women with GDM history. Conclusions: Breastfeeding was associated with lower T2D and CVD risks among women with GDM history, suggesting some shared risk factors or etiologies across reproductive lifespan and long-term cardiometabolic health. Ages at menarche and 1 st birth showed differential associations with T2D and CVD.
Abstract P556: Temporal and Global Trends of the Incidence of Sudden Cardiac Death in Hypertrophic Cardiomyopathy: A Meta-Analysis
Authors: Omar M Abdelfattah, Matthew Martinez, Ahmed Sayed, Mohamed ElRefaei, Abdelrahman Abushouk, Ahmed Hassan, Ahmad Masri, Stephen L Winters, Samir Kapadia, Barry Maron, Ethan J Rowin, Martin Maron
Journal: Circulation (2023)

Introduction: Since hypertrophic cardiomyopathy(HCM) initial description, sudden cardiac death (SCD) has been the most feared complication of HCM. Hypothesis: Temporal, geographical, and age-related trends of SCD rates in HCM have drastically decreased over time. Methods: Databases were systematically searched to Nov 2021 for studies reporting on SCD event rates in HCM. Patients with SCD equivalents (appropriate ICD shocks and non-fatal SCD) were excluded. Random-e!ects model was utilized to pool study estimates calculating the overall incidence rates(IR) for each time-era, geographical region, and age-group. We analyzed 2 eras (before vs. after 2000, following implementation of ICD in HCM). Following 2000, 5-year intervals were used to reflect the temporal change in SCD. Results: 98 studies(N=70,510patients and 431,407patient-years) met inclusion criteria. Overall rate of HCM SCD was 0.43%/year (95% CI: 0.37-0.50%; I2=75%; SCD events:1,938; person-years of follow-up: 408,715), with young patients(&lt;18 years) demonstrating a&gt;2-fold-risk for SCD vs. adults(18- 60years) (IR:1.09%; 95% CI: 0.69-1.73% vs. IR: 0.43%; 95% CI: 0.37-0.50%)(P-value for subgroup di!erences:&lt;0.01). Contemporary SCD rates from 2015-present were 0.32%/year; significantly lower compared to 2000 or earlier (IR: 0.32%; 95% CI:0.20-0.52%, vs. IR: 0.73%; 95% CI:0.53-1.02%,respectively). Reported HCM-SCD rates were lowest in North America (IR: 0.28%;95% CI:0.18-0.43%) and highest in Asia(IR: 0.67%; 95% CI:0.54-0.84%). Conclusions: Contemporary HCM-related SCD are low (0.32%/year) representing a 2-fold decrease compared to prior treatment eras, with young HCM patients at the highest risk. SCD risk stratification maturation and primary prevention ICD application are likely responsible for the notable decline in SCD trends. Moreover, worldwide geographical disparities in SCD was evident, underscoring the need to increase access to SCD prevention for all HCM patients.
Abstract P341: A Flexible, Interpretable Approach to Recalibrate Risk Prediction Models: Adapting the Pooled Cohorts Equation to a Local New England Contemporary Population
Authors: Aniket N Zinzuwadia, Olga Mineeva, Chunying Li, Lin Chen, Brian Cade, Elizabeth Karlson, Zareen Farukhi, Nina Paynter, Samia Mora, Olga Demler
Journal: Circulation (2023)

Introduction: Atherosclerotic cardiovascular disease (ASCVD) prognostic models have well-documented poor generalizability in contemporary populations. Sustained, accurate performance of risk prediction models is challenging given demographic shifts, changes in practice patterns, and geographic variation. We propose an approach to tailor known risk prediction models for local settings while preserving known disease risk mechanisms. Here, as a case study, we recalibrate the Pooled Cohort Equations (PCE) in a contemporary (1997-2018), local electronic health records (EHR) cohort in New England. Methods: We conducted a retrospective cohort study using EHR from large Boston-area hospitals. 61,808 patients 45+ years old, without ASCVD in 1997-2006 and complete data to calculate PCE model were split into training (50%), validation (10%), and test sets (40%). We used XGBoost to recalibrate PCE model (XGB-PCE) using PCE risk score, age, race/ethnicity, and sex (Figure). We constrained the XGB-PCE model to preserve known physiologic trends i.e. increase in ASCVD risk with increase in total cholesterol and systolic blood pressure. Models’ discrimination and calibration were calculated in a set aside test set using the Harrell’s c-index and modified Nam D’Agostino χ2 test. Results: In the test set, XGB-PCE exhibited improved calibration across ASCVD risk categories (p=0.37) and race/ethnicity populations (p=0.73). In contrast, even after recalibration in the large, PCE was poorly calibrated across risk categories (p&lt;0.001) and race/ethnicity populations (p&lt;0.001). For model discrimination, both models produced similar c-index (Δc-index of ±.01). Conclusions: Our recalibration approach maintained comparable discriminative performance and demonstrated improved calibration relative to the PCE while preserving known disease risk mechanisms. Methods that are flexible and preserve disease mechanisms have the potential to locally tailor existing models to be better calibrated for contemporary populations.
Increased RTN3 phenocopies nonalcoholic fatty liver disease by inhibiting the AMPK–IDH2 pathway
Authors: Hao Huang, Shuai Guo, Ya‐Qin Chen, Yu‐Xing Liu, Jie‐Yuan Jin, Yun Liang, Liang‐Liang Fan, Rong Xiang
Journal: MedComm (2023)

Abstract Reticulon 3 (RTN3), an endoplasmic reticulum protein, is crucial in neurodegenerative and kidney diseases. However, the role of RTN3 in liver tissues has not been described. Here, we employed public datasets, patients, and several animal models to explore the role of RTN3 in nonalcoholic fatty liver disease (NAFLD). The underlying mechanisms were studied in primary hepatocytes and L02 cells in vitro. We found an increased expression of RTN3 in NAFLD patients, high‐fat diet mice, and oxidized low‐density lipoprotein‐treated L02 cells. The RTN3 transgenic mice exhibited the phenotypes of fatty liver and lipid accumulation. Single‐cell RNA sequencing analysis indicated that increased RTN3 might induce mitochondrial dysfunction. We further showed this in primary hepatocytes, the L02 cell line, and the Caenorhabditis elegans strain. Mechanistically, RTN3 regulated these events through its interactions with glucose‐regulated protein 78 (GRP78), which further inhibited the adenosine 5 monophosphate‐activated protein kinase (AMPK)–isocitrate dehydrogenase 2 (IDH2) pathway. In the end, knockout of RTN3 relieved fatty liver and mitochondrial dysfunction. Our study indicated that RTN3 was important in NAFLD and lipid catabolism and that an increase in RTN3 in the liver might be a risk factor for nonalcoholic steatohepatitis and NAFLD.
Abstract P564: Prevalence of Metabolic Syndrome in a Young Sub-Saharan African Community
Authors: Mame Awa Sene, Ibrahima Bara Diop, Audrey Geoffroy, Awa Ba, Sidy Seck, Mor Diaw, Gabriel S Tajeu, Xavier Jouven, Bamba Gaye
Journal: Circulation (2023)

Background: Metabolic syndrome is known as a predictor of cardiovascular disease (CVD), a leading cause of death globally. The factors that comprise metabolic syndrome are on the rise in Sub-Saharan Africa, and data regarding the prevalence of metabolic syndrome in communities of aged less than 40 years old remain scarce. Methods: Data were collected between March and April 2013 from 3 regions of the Northern Senegal (i.e., Saint-Louis, Matam et and Louga) using a cluster sampling method and the survey base of the national statistical and demographical agency. Subjects aged between 18 and 80 years were recruited, however, the present study focused on adult populations below 40 years of age. Participants underwent a face-to-face questionnaire to collect demographics and data on cardiovascular history/risk factors. Blood pressure (BP) and anthropometric measurements were performed in addition to a blood test measuring fasting triglycerides, high density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and plasma glucose. Metabolic syndrome was defined as fasting plasma glucose ≥110 mg/dl, serum triglycerides ≥150 mg/dl, serum HDL cholesterol &lt;40 mg/dl, BP ≥130/85 mmHg or on BP medication, or waist girth &gt;102 cm in males or &gt;89 cm in females. Comparisons used the χ2 test for categorical variables and Student’s t test for continuous variables. Multiple logistic regression was used to identify factors associated with CFI, after considering potential confounders. Covariates with significant association (P&lt;0.05) in univariate analysis were included in the multivariate logistic model. Results: Of the 2,440 subjects recruited, 1080 participants were less than 40 years old and included in the current analysis. The mean age of these participants was 31 ± 7.53I. There were 296 (27%) male participants in our study. . Overall, there were 41 participants (3.8%) with metabolic. For individual components of metabolic syndrome, body mass index of 25 or higher was present in 32% of the population with a significant increase among women (38 vs 15% vs 3,7%, p&lt;0,001). The prevalence of hypertension was28% and more than half of the population presented with dyslipidaemia (554 participants). Among those with dyslipidemia, 339 have a high total cholesterol index (61%, 95% CI: 57-65%). Conclusion: Our community-based cross-sectional study revealed a low prevalence of metabolic syndrome among younger participants in northern Senegal. However, the prevalence of dyslipidaemia was high.
Abstract P224: The Collaborative, Iterative Process of Changing Diet Toward Plant Proteins: A Qualitative Study Exploring the Drivers and Process of Dietary Change
Authors: Vijaya Parameswaran, Corinne Coen, Phillip Cola, Rajesh Dash, Kurt Stange, Kalle Lyytinen
Journal: Circulation (2023)

Background: Psychological models describe dietary change as linear, self-regulatory, and outcome driven. Yet, the average adult tries at least two diets a year and abandons them after a few days. The cardiometabolic benefits of plant proteins (PP) are undisputed, but changing protein choices can be challenging. Methods: We recruited 30 adults who changed their protein choice using snowball sampling and conducted inductive semi-structured interviews to understand why and how protein choices shift, who influences them, and whether they stick. Participants shared influencer names, the extent of influence (high-3, medium-2, low-1), and their rationale regarding food decisions. We transcribed and analyzed the interviews to identify common themes and mapped their social network. Results: (90%) 27/30 identified at least two PP sources, (33%) 10/30 entirely replaced animal protein (AP) with PP, (57%) 17/30 decreased AP intake significantly but did not replace it with PP, (10%) 3/30 increased AP sources. All reported continuing change for at least six months. Our analysis, Figure 1, uncovers a mindful process of change that is collaborative, continuous, iterative, and adaptive, anchored in three dimensions: 1) Crafting the milieu - personal and social environment: 2) Discovering social self - cultivating psychosocial awareness thru practice and reflection: and 3) Sociotechnical art - acquiring culinary knowledge from others. Social network analysis (SNA) revealed three boundary spanners connecting more than one group, betweenness (&gt;0.4), three popular participants, eigencentrality (&gt;0.5) and many community formations, modularity (0.82), Figure 2. Conclusion: Based on our results, people who desire change gravitate toward those who have successfully navigated it. The process of dietary change reveals opportunities to tailor diets supporting close family and connections. Identifying and targeting diet recommendations towards influencers in local communities may help achieve widespread and long-lasting change.
Abstract P581: Body Mass Index Variability in Relation to Heart Failure and Outcomes
Authors: Chang Liu, Yiyun Chiang, Qin Hui, Peter Wilson, Jacob Joseph, Yan Sun
Journal: Circulation (2023)

Introduction: Heart failure (HF) is a disease with high morbidity and mortality, and affects an estimated total of 6.2 million HF patients in the US. Obesity is an established risk factor for HF, and fluctuation in body mass index (BMI) has shown a negative effect in health. Hypothesis: We assessed the hypothesis that BMI variability is associated with incident HF. Methods: This study used data from the UK Biobank, which is a prospective cohort study with a median follow-up of 12.5 years. After excluding prevalent HF or cancer at enrollment, a total of 99,368 White participants with ≥ 3 BMI measures from primary care records within &gt; 2 years before and at enrollment were included. The within-participant variability of BMI was evaluated using standard deviation (SD) and coefficient of variation (CV), which were converted to z scores for further analysis. HF prevalence and incidence were ascertained based on in-patient Hospital Episode Statistics using ICD-9 and -10 codes and self-report at enrollment. The association of BMI variability with incident HF was assessed using Fine and Gray's competing risk model, treating death events obtained from the National Death Registry as competing risk. Two multi-variate models were used: Model 1 adjusted for age, sex, smoking history, alcohol consumption, diabetes, hypertension, history of heart attack or stroke, lipids, estimated glomerular filtration rate; Model 2 additionally adjusted for mean BMI across multiple measures per individual. Sex-stratified analyses were also conducted. Results: The cohort was 43% male, with mean age 57.5 (SD 7.8) years. A total of 3,406 incident HF cases were observed during the follow-up. Per SD higher in BMI variability measured in SD and CV were associated with higher risk in HF incidence, with stronger associations observed among females, Figure 1 . Conclusions: BMI fluctuation is linked with HF incidence. Future studies are warranted to explore the mechanisms in changes of BMI such as body composition, and the possible causal pathways leading to HF.
Abstract 60: Impact of a Multisite, Protocol-Driven, Nurse Practitioner-Led, Cardiovascular Prevention Program in a Hispanic Medicare Advantage Population at High Risk for ASCVD: Healthy Heart Program at Cano Health.
Authors: Veronica MCCLOSKEY, Khurram Nasir, Rohan Khera, Evangelos K Oikonomou, Robert Diaz, Robert Kenney, Richard Aguilar, Martha Gulati, Oscar H Cingolani, Ty J Gluckman, Ron Blankstein, Marlow B Hernandez, Juan Rivera
Journal: Circulation (2023)

Introduction: Despite availability of effective and inexpensive pharmacologic therapies for hypercholesterolemia and hypertension, many patients at high risk for atherosclerotic cardiovascular disease (ASCVD) do not achieve optimal low-density lipoprotein (LDL) and systolic blood pressure (SBP) levels. We hypothesized that risk factor control could be improved by using nurse practitioners and a guideline-directed protocol in a Medicare Advantage (MA) population. Methods: We designed and implemented an ongoing 18 site, multistate (FL, TX, NV), ASCVD risk assessment and management program (Healthy Heart) in a large national MA primary care clinic (Cano Health). The cardiometabolic risk assessment and management program was designed by a team of preventive cardiologists, with the plan of being Nurse Practitioner (NP)-led, with remote support by a cardiologist. Protocols provided details on initiation and titration of drug therapy to achieve LDL-C and SBP goals. Patients with organ transplants, advanced cancer, an ejection fraction &lt;35%, and on hemodialysis were excluded. Results: From October 2021-October 2022, 5430 patients were enrolled in the program. A total of 1858 (34.2%) had established ASCVD, 1033 (19.0%) had diabetes mellitus (DM). A total of 713 (13.1%) had both ASCVD and DM. In patients who had ASCVD and diabetes together, high intensity statin use increased from 39.4% to 68.3% after enrollment; 52.66% achieved an LDL-C &lt;70 mg/dl after enrollment compared to 31.0% at baseline. Antihypertensive medications were intensified in 408/1041 (39.2%) of ASCVD and 276/558 (49.5%) of DM patients, with a higher proportion achieving a SBP &lt;130 mm Hg after enrollment. Conclusions: Implementing a novel cardiovascular prevention program in a population of mostly Hispanic MA patients at high risk for ASCVD, using NPs, with strict adherence to a step-by-step evidence-based protocol supervised by cardiologists, is associated with reduction in LDL levels and SBP and with improvement in reaching LDL and SBP targets.
Abstract P342: Periodontal Disease is Associated With Elevated Prediabetes Prevalence and Glucose Levels Among Non-Diabetic Adults. Results From Oral Infections, Glucose Intolerance and Insulin Resistance Study
Authors: Hamdi S Adam, Rebecca L Molinsky, Sumith Roy, Michael Rosenbaum, Bruce Paster, Melana Yuzefpolskaya, Paolo C Colombo, Panos N Papapanou, Moise Desvarieux, David R Jacobs, Ryan T Demmer
Journal: Circulation (2023)

Background: Periodontitis (a bacterially-driven, inflammatory disease) is a plausible risk factor for prediabetes and diabetes. We studied the association between clinical attachment loss (CAL – a cumulative measure of tooth-supporting tissues lost due to periodontitis), prediabetes, and glucose levels among non-diabetic younger adults. Hypothesis: We hypothesize that greater CAL is associated with higher levels of biomarkers of cardiometabolic risk cross-sectionally. Methods: We included n=1071 non-diabetic participants from the Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) who underwent full-mouth periodontal examinations and provided fasting blood at baseline. Baseline enrollment occurred in two waves: Wave 1 (2011-2013; n=293) and Wave 2 (2016-2020; n=778). HbA1c and glucose were measured during clinical exams. Prediabetes was defined as fasting glucose between 100-125 mg/dL or HbA1c between 5.7-6.4% per American Diabetes Association guidelines. We computed prevalence ratios and 95% confidence intervals of prediabetes among 2 nd and 3 rd CAL tertiles (vs. 1 st tertile) via multivariable Poisson regression with robust variance estimation. Multivariable linear regression was used to assess the association between CAL tertiles (independent variable) and estimates of glucose and HbA1c. We adjusted for demographics, health variables, and study wave. Results: The mean age(SD) of participants was 32.3(9.6) years and 28% were male. Prediabetes prevalence was 8.7%. Multivariable adjusted prevalence ratios (95%CIs) for prediabetes in tertiles 2 and 3 (vs. 1) were 1.45(0.79,2.67) and 1.91(0.99,3.67), respectively, consistent with p for trend = 0.05 and stronger associations with continuous glucose and HbA1c (see Table ). Conclusion: CAL, a cumulative measure of periodontitis, was cross-sectionally associated with increased prediabetes prevalence, glucose and HbA1c.